19.3 Organ Transplantation and Rejection
3 min read•june 18, 2024
Organ is a life-saving procedure, but it comes with challenges. The body's immune system can reject foreign tissues, making matching donor and recipient crucial. play a key role in this process, helping determine compatibility.
Different types of grafts exist, each with unique risks. use a person's own tissue, while come from others. GVHD is a serious complication in some transplants, where donor cells attack the recipient's body.
Organ Transplantation and Immune Responses
Role of HLAs in transplantation
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- are cell surface proteins encoded by the major complex () genes responsible for presenting antigenic peptides to T cells and play a crucial role in self-recognition and immune response initiation ( recognize peptides presented by MHC class I molecules, while recognize peptides presented by MHC class II molecules)
- HLA matching between donor and recipient is essential for successful organ as closer HLA matches reduce the risk of , while HLA mismatches can lead to immune-mediated rejection of the transplanted organ (kidneys, hearts, livers)
- HLA typing is performed before transplantation to assess compatibility using serological and molecular methods to determine HLA alleles, and cross-matching is done to detect preformed antibodies against donor HLAs
- Immunosuppressive drugs are used to prevent rejection in HLA-mismatched transplants by suppressing the recipient's immune response to the foreign HLAs ( like and , like , and anti-proliferative agents like )
Types of tissue grafts
- Autografts are tissues transplanted from one site to another within the same individual and do not elicit an immune response as they are self-tissues (skin grafts for burn victims, bone grafts in orthopedic surgery)
- Allografts (homografts) are tissues transplanted between genetically non-identical individuals of the same species and can elicit an immune response due to HLA mismatches (kidney, heart, liver, and bone marrow transplants)
- (heterografts) are tissues transplanted between different species and provoke a strong immune response due to significant genetic differences, making them uncommon in clinical settings due to high rejection rates (porcine heart valves, bovine pericardial patches)
- are tissues transplanted between genetically identical individuals ( twins) and do not elicit an immune response as they share the same HLA alleles, but are rare due to the limited availability of genetically identical donors
Causes and consequences of GVHD
- is a complication that can occur after allogeneic (HSCT) when immunocompetent donor T cells recognize the recipient's tissues as foreign and mount an immune response, more likely to occur when there are HLA mismatches between the donor and recipient
- typically develops within the first 100 days post-transplant and affects the skin (rash), liver (jaundice), and gastrointestinal tract (diarrhea, abdominal pain)
- develops later (>100 days post-transplant) and can affect multiple organs, resembling autoimmune disorders and causing skin changes, dry mouth and eyes, and lung dysfunction
- Prevention and treatment of GVHD involve immunosuppressive drugs (prophylactic to reduce risk, corticosteroids, calcineurin inhibitors, and other immunomodulatory agents for treatment) and supportive care
- is a beneficial aspect of GVHD in the context of HSCT for hematological malignancies (leukemias, lymphomas) where donor T cells can recognize and eliminate residual tumor cells in the recipient, helping prevent disease relapse post-transplant
Transplantation and Immune Responses
- Rejection occurs when the recipient's immune system recognizes the transplanted organ as foreign and mounts an immune response against it
- Immunosuppression is used to prevent rejection by suppressing the recipient's immune system, but it can increase the risk of infections and certain cancers
- is the ideal outcome in transplantation, where the recipient's immune system accepts the transplanted organ without the need for long-term immunosuppression
- Histocompatibility refers to the degree of similarity between the donor's and recipient's HLA antigens, which affects the likelihood of successful transplantation
Key Terms to Review (48)
Acute GVHD: Acute Graft-Versus-Host Disease (GVHD) is a condition where donor immune cells attack the recipient's tissues following an organ or bone marrow transplant. It typically occurs within the first 100 days post-transplant.
Acute GVHD: Acute graft-versus-host disease (GVHD) is a serious complication that can occur after an allogeneic stem cell or organ transplant. It arises when the transplanted immune cells (the graft) recognize the recipient's tissues (the host) as foreign and mount an aggressive immune response against them.
Allograft: An allograft is a tissue or organ transplant from a donor to a genetically non-identical recipient of the same species. Successful transplantation requires careful matching and immunosuppressive therapy to prevent rejection.
Allografts: Allografts are tissues or organs that are transplanted from one individual to another of the same species, but with a different genetic makeup. They are a crucial component in the field of organ transplantation, where they are used to replace damaged or failing organs in recipients.
Autograft: An autograft is a tissue or organ transplant where the donor and recipient are the same person. This type of graft reduces the risk of immune rejection.
Autografts: An autograft is a surgical procedure where tissue is transplanted from one part of a person's body to another part of the same person's body. This type of graft is commonly used in the context of organ transplantation and the management of tissue damage or loss.
Bone marrow transplant: A bone marrow transplant is a medical procedure that replaces damaged or destroyed bone marrow with healthy bone marrow stem cells. It is often used to treat certain cancers and disorders of the blood and immune system.
Calcineurin Inhibitors: Calcineurin inhibitors are a class of immunosuppressant drugs that work by blocking the activity of the enzyme calcineurin, which is essential for the activation and proliferation of T cells. These drugs are commonly used to prevent organ rejection in transplant recipients.
Cancer: Cancer is a disease characterized by the uncontrolled division and spread of abnormal cells within the body. It can disrupt normal immune system functions and evade immune responses.
CD4 T cells: CD4 T cells are a type of white blood cell that play a crucial role in the immune system by helping to coordinate the body's response to infections. They are also known as helper T cells and are essential in fighting off both viral and bacterial infections.
CD4+ T cells: CD4+ T cells, also known as helper T cells, are a type of lymphocyte that plays a crucial role in the adaptive immune response. These cells express the CD4 co-receptor on their surface, which helps them recognize and respond to antigens presented by major histocompatibility complex (MHC) class II molecules on the surface of antigen-presenting cells.
CD8+ T cells: CD8+ T cells, also known as cytotoxic T cells, are a subset of T lymphocytes that play a crucial role in the adaptive immune response by directly killing infected or cancerous cells. They recognize antigens presented by major histocompatibility complex (MHC) class I molecules on the surface of target cells and initiate a cytotoxic response to eliminate these threats.
Central tolerance: Central tolerance is a critical process occurring in the thymus where developing T lymphocytes (T cells) that recognize self-antigens with high affinity are eliminated through negative selection, preventing autoimmune responses.
Chronic GVHD: Chronic Graft-Versus-Host Disease (GVHD) is a long-term complication that can occur after an allogeneic stem cell or bone marrow transplant, where the donor's immune cells attack the recipient's tissues. It typically develops more than 100 days post-transplant and can affect multiple organs.
Chronic GVHD: Chronic GVHD (Graft-Versus-Host Disease) is a complex and potentially life-threatening complication that can occur after an allogeneic stem cell or organ transplant. It arises when the transplanted immune cells (the graft) recognize the recipient's tissues (the host) as foreign and mount an autoimmune-like attack against them.
Corticosteroid: Corticosteroids are a class of steroid hormones that reduce inflammation and modulate the immune response. They are often used to treat hypersensitivities, autoimmune disorders, and to prevent organ rejection after transplantation.
Corticosteroids: Corticosteroids are a class of steroid hormones that are produced naturally in the adrenal glands or can be synthetically manufactured. They play a crucial role in regulating various physiological processes, including immune function, inflammation, and organ transplantation.
Cyclosporine: Cyclosporine is an immunosuppressant drug used to prevent organ rejection in transplant recipients. It works by inhibiting the activation and proliferation of T-cells, a key component of the body's immune response, thereby reducing the likelihood of the transplanted organ being rejected.
Cytokine storm: A cytokine storm is an excessive and uncontrolled release of pro-inflammatory cytokines, often resulting from an overactive immune response. It can lead to severe inflammation and tissue damage, particularly in the respiratory system.
Graft: A graft is a tissue or organ transferred from one site to another, either within the same individual or between donor and recipient. It plays a crucial role in organ transplantation.
Graft-versus-Host Disease: Graft-versus-host disease (GVHD) is a complication that can occur after an allogeneic stem cell or organ transplant, where the donated immune cells from the graft (the transplanted tissue) attack the recipient's healthy cells, mistaking them as foreign. This can lead to significant tissue damage and life-threatening complications.
Graft-versus-host disease (GVHD): Graft-versus-host disease (GVHD) is a medical condition that occurs when donor immune cells attack the recipient's tissues after an organ or bone marrow transplant. It primarily affects the skin, liver, and gastrointestinal tract.
Graft-versus-Tumor Effect: The graft-versus-tumor effect refers to the ability of donor immune cells within a transplanted organ or tissue to recognize and attack cancer cells in the recipient's body. This phenomenon can be harnessed in certain cancer treatments to help eliminate malignant cells.
Hematopoietic stem cell: Hematopoietic stem cells are multipotent stem cells that give rise to all blood cell types, including myeloid and lymphoid lineages. They play a crucial role in the body's ability to regenerate and maintain the blood and immune systems.
Hematopoietic Stem Cell Transplantation: Hematopoietic stem cell transplantation is a medical procedure that involves replacing damaged or destroyed blood-forming stem cells with healthy stem cells, often used to treat certain types of cancer and other blood disorders.
Histocompatibility: Histocompatibility refers to the degree of genetic similarity between individuals, which determines the likelihood of an organ or tissue transplant being accepted or rejected by the recipient's immune system. It is a crucial factor in the success of organ transplantation procedures.
HLAs: HLAs, or Human Leukocyte Antigens, are a group of proteins found on the surface of most cells in the human body. They play a crucial role in the immune system's ability to recognize self from non-self, which is essential for organ transplantation and preventing rejection.
Human leukocyte antigens (HLAs): Human leukocyte antigens (HLAs) are proteins found on the surface of most cells in the body that help the immune system distinguish between self and non-self. They play a crucial role in organ transplantation by influencing graft acceptance or rejection.
Immunosuppressant drug: Immunosuppressant drugs are medications that inhibit or prevent activity of the immune system. They are commonly used to prevent organ rejection in transplant patients.
Immunosuppression: Immunosuppression refers to the reduction or inhibition of the normal immune response, either through natural means or through medical intervention. This can have significant implications in various areas of health and disease.
Isograft: An isograft is a type of tissue or organ transplant between genetically identical individuals, such as identical twins. This minimizes the risk of immune rejection due to the genetic similarity.
Isografts: Isografts refer to organ or tissue transplants between genetically identical individuals, such as identical twins. They are a type of allograft, which is a transplant between two genetically distinct individuals of the same species.
Lupus: Lupus is a chronic autoimmune disease where the immune system attacks healthy tissues, causing widespread inflammation and damage. It can affect various organs, including the skin, joints, kidneys, brain, and other parts of the body.
Major histocompatibility complex markers: Major histocompatibility complex (MHC) markers are proteins found on the surface of cells that help the immune system recognize foreign substances. They play a crucial role in organ transplantation and can trigger immune responses that may lead to rejection.
MHC: MHC, or Major Histocompatibility Complex, is a set of genes that encode proteins responsible for regulating the immune system's ability to recognize and respond to foreign substances within the body. These proteins are crucial in the context of organ transplantation and rejection, as they play a central role in the body's acceptance or rejection of a transplanted organ.
MHC I: MHC I (Major Histocompatibility Complex Class I) molecules are cell surface proteins essential for the immune system to recognize infected or abnormal cells. They present endogenous antigens to cytotoxic T lymphocytes, initiating an immune response.
MHC II: MHC II (Major Histocompatibility Complex class II) are proteins found on the surface of certain immune cells that present antigens to T-helper cells. They play a crucial role in initiating the immune response by displaying foreign peptides to T cells.
Monozygotic: Monozygotic refers to twins that originate from a single fertilized egg which splits into two embryos. These twins are genetically identical and share the same DNA.
Mycophenolate mofetil: Mycophenolate mofetil is an immunosuppressant drug primarily used to prevent organ rejection in transplant recipients. It works by inhibiting the proliferation of T and B lymphocytes, key players in the immune response that can lead to graft rejection.
Prednisone: Prednisone is a synthetic corticosteroid drug commonly used to reduce inflammation and suppress the immune system. It is often prescribed for conditions involving hypersensitivities and autoimmune diseases.
Prednisone: Prednisone is a synthetic corticosteroid medication that is used to treat a wide range of medical conditions by reducing inflammation and suppressing the immune system. It is a key drug in the management of organ transplantation and fungal infections of the reproductive system.
Rejection: Rejection is the immune system's response to a foreign object or tissue, such as a transplanted organ, that is recognized as non-self and triggers an attack to eliminate it. This is a critical concept in the context of organ transplantation and the body's defense mechanisms.
Tacrolimus: Tacrolimus is an immunosuppressant drug primarily used to prevent rejection in organ transplant recipients. It works by inhibiting the activity of calcineurin, a key enzyme involved in the activation of T cells, thereby reducing the immune system's ability to mount a rejection response against the transplanted organ.
Tolerance: Tolerance refers to the ability of an individual or organism to withstand or accept a particular substance, condition, or treatment without adverse effects. This concept is crucial in the context of hypersensitivities and organ transplantation, as it describes the body's capacity to adapt and respond to various stimuli or foreign entities.
Transplantation: Transplantation is the process of transferring cells, tissues, or organs from one site to another. It is commonly used to replace damaged or failing organs in patients.
Transplantation: Transplantation is the surgical process of transferring an organ, tissue, or cells from one part of the body to another, or from one individual to another. It is a critical medical procedure used to replace damaged or diseased organs, tissues, or cells with healthy ones to restore normal function and improve the recipient's quality of life.
Xenograft: A xenograft is a transplant of organs, tissues, or cells from one species to another. It is commonly used in research and has potential for clinical applications.
Xenografts: Xenografts refer to the transplantation of organs or tissues from one species to another, such as from an animal to a human. This is a critical concept in the context of organ transplantation and the body's immune response to foreign tissues.